title: A high-fat/high-cholesterol diet inhibits growth of fetal hippocampal transplants via increased inflammation.
abstract: A diet containing high levels of saturated fat and cholesterol is detrimental to many aspects of health and is known to lead to obesity, metabolic syndrome, heart disease, diabetes, and cancer. However, the effects of a diet rich in saturated fat and cholesterol on the brain are not  currently well understood. In order to determine direct effects of a high saturated fat and cholesterol diet upon fetal hippocampal tissue, we transplanted hippocampal grafts from embryonic day 18 rats to the anterior eye chamber of 16-month-old host animals that were fed either a normal rat  chow diet or a 10% hydrogenated coconut oil + 2% cholesterol diet (HFHC diet) for 8 weeks. One eye per rat received topical application of an IL-1 receptor antagonist (IL-1Ra, Kineret®) and the other served as a saline control. Results revealed that the HFHC diet led to a marked reduction  in hippocampal transplant growth, and detrimental effects of the diet were alleviated by the IL-1 receptor antagonist IL-1Ra. Graft morphology demonstrated that the HFHC diet reduced organotypical development of the hippocampal neuronal cell layers, which was also alleviated by IL-1Ra. Finally,  grafts were evaluated with markers for glucose transporter expression, astrocytes, and activated microglia. Our results demonstrate significant effects of the HFHC diet on hippocampal morphology, including elevated microglial activation and reduced neuronal development. IL-1Ra largely blocked  the detrimental effects of this diet, suggesting a potential use for this agent in neurological disorders involving neuroinflammation.
authors.affiliation: Department of Neurosciences and the Center on Aging, Medical University of South Carolina, Charleston, SC, USA. Linnea.Freeman@pbrc.edu
authors.forename: L R
authors.initials: LR
authors.lastname: Freeman
authors.forename: B J
authors.initials: BJ
authors.lastname: Small
authors.forename: P C
authors.initials: PC
authors.lastname: Bickford
authors.forename: C
authors.initials: C
authors.lastname: Umphlet
authors.forename: A-Ch
authors.initials: AC
authors.lastname: Granholm
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects; D002791:Cholesterol, Dietary / Q000009:adverse effects*; D004041:Dietary Fats / Q000009:adverse effects*; D004435:Eating / Q000187:drug effects; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000196:embryology / Q000637:transplantation*; D007249:Inflammation / Q000139:chemically induced*; D053590:Interleukin 1 Receptor Antagonist Protein / Q000627:therapeutic use*; D017628:Microglia / Q000187:drug effects; D051381:Rats
chemical_list: D002791:Cholesterol, Dietary; D004041:Dietary Fats; D053590:Interleukin 1 Receptor Antagonist Protein